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Naloxegol an Investigational Drug for the Treatment of Opioid -Induced Constipation

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Naloxegol an Investigational Drug for the Treatment of Opioid -Induced Constipation Naloxegol an investigational drug for the treatment of Opioid -Induced Constipation October 2012 Cautionary Statement Regarding FdForward-LkiSttLooking Statement s In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act 1995, we are providing the following cautionary statement: This presentation contains certain forward-looking statements with respect to the operations , performance and financial condition of the Group. Although we believe our expectations are based on reasonable assumptions, any forward-looking statements, by their very nature, involve risks and uncertainties and may be influenced by factors that could cause actual outcomes and results to be materially different from those predicted. The forward-looking statements reflect knowledge and information available at the date of preparation of this presentation and AstraZeneca undertakes no obligation to update these forward-looking statements. We identify the forward-looking statements by using the words 'anticipates', 'believes', 'expects', 'intends' and similar expressions in such statements. Important factors that could cause actual results to differ materially from those contained in forward-looking statements, certain of which are beyond our control, include, among other things: the loss or expiration of patents, marketing exclusivity or trade marks, or the risk of failure to obtain patent protection; the risk of substantial adverse litigation/government investigation claims and insufficient insurance coverage; exchange rate fluctuations; the risk that R&D will not yield new products that achieve commercial success; the risk that strategic alliances and acquisitions will be unsuccessful; the impact of competition, price controls and price reductions; taxation risks; the risk of substantial product liability claims; the impact of any failure by third parties to supply materials or services; the risk of failure to manage a crisis; the risk of delay to new product launches; the difficulties of obtaining and maintaining regulatory approvals for products; the risk of failure to observe ongoing regulatory oversight; the risk that new products do not perform as we expect; the risk of environmental liabilities; the risks associated with conducting business in emerging markets; the risk of reputational damage; the risk of product counterfeiting; the risk of failure to successfully implement planned cost reduction measures through productivity initiatives and restructuring programmes; the risk that regulatory approval processes for biosimilars could have an adverse effect on future commercial prospects; and the impact of increasing implementation and enforcement of more stringent anti-bribery and anti-corruption leg is la tion. No thing in this presen ta tion s hou ld be cons true d as a pro fit forecas t. 2 Introduction and Overview Section Speaker Introduction Kathy Cantagallo naloxegol VP, Development Overview of the Opioid Market Mike Gibbs VP Brand Marketing Naloxegol: Overview of the Mark Sostek, M.D. molecule and its development Executive Director, Development Overview and Summary Kathy Cantagallo naloxegg,ol VP, Develop ment Q&A 3 Introduction Key Facts AstraZeneca and Nektar Therapeutics entered into an exclusive worldwide license agreement for naloxegol on 21 September 2009 . AstraZeneca has development and commercialization rights for naloxegol (previously NKTR-118). Nektar received an upfront 1 payment of $125m . Naloxegol is a once a day oral, peripherally acting, μ-opioid receptor antagonist under investigation for the treatment of constipation as a side effect of prescription opioid pain medicines 2 (“opioid-induced constipation” or OIC). The core Phase III KODIAC program for naloxegol comprises four clinical studies which are designed to investigate the safety and efficacyyg of naloxegol for the chronic treatment of OIC in patients 3 with non-cancer related pain: •We anticipate having high level results for the Phase III program in Q4 2012. 4 Opioid Market Overview Worldwide total opioid sales and volume* Sales Standard Units ($mil) (mil) $15,000 39,500 $14,500 38,500 $14,000 37,500 $13, 500 $13,000 36,500 $12,500 35,500 MAT MAT MAT MAT MAT MAT MAT MAT MAT MAT Q2/08 Q2/09 Q2/10 Q2/11 Q2/12 Q2/08 Q2/09 Q2/10 Q2/11 Q2/12 Approximately 85% of opioid volume is long-term use (>30days)** Leading diagnoses for opioid use*** Chronic Back Pain Osteoarthritis Neuropathic Pain Cancer Pain Fibromyalgia (24)% (15)% (4)% (4)% (1)% *Source: IMS MDART MAT-2Q12 **Source: NKTR-118 OIC Patient Quantitative Study, Mar-2010 US, UK, Ger, Fra, Can ***Source: IMS Medical Database, MAT @Q2012; based on Rxs by diag; other diags account for less than 1% each but add up to the other 50%; US, UK, Ger, Fra, Can The opioid market is dominated by US, Canada, France, Germany and UK* Sales Standard Units ($mil) (mil) ALL ALL OTHER OTHER 19. 5% JAPAN 21. 0% JAPAN 0.4% 3.3% U. S. CANADA 49.3% CANADA 4.8% 4.4% U. S. 54. 3% FRANCE 4.8% FRANCE 5.1% UK UK 5.4% 14.0% GERMANY 8.4% GERMANY N = $14.8 bn5.3% N = 39.5 bn *IMS MDART MAT-2Q12. Opioid Induced Constipation Mechanism of Opioid-Induced Constipation Although highly effective in the control of pain, the use of opioids is associated with a key side effect - constipation1 – affecting Opioids bind to μ-opioid receptors in GI tract 40-50% of patients.2 GI motility, secretion, fluid absorption, and blood Constipation can negatively impact patient flow are affected quality of life3 and may result in patients avoiding or discontinuing pain therapy with Colonic transit delayed strong opioids, compromising effective analilgesia.1341,3,4 Sphincter tone increases OIC is often overlooked and inadequately Defecation inhibited managed.5,6,7 Whilst conventional laxatives can be used in conjunction with opioids to alleviate OIC symptoms, they do not treat the cause of the problem3 and often do not achieve the desired treatment outcome. 1,8 1Bell TJ et al. Pain Medicine. 2008 6 Tittle Met al. Am J Crit Care. 1994 2Yuan CS et al. 2005 Handbook of Opioid Bowel Syndrome 7 Pappagallo M. Am J Surg. 2001 3 Panchal SJ et al. Int J Clin Pract. 2007 8 Holzer Regulatory Peptides 155 (2009) 11-17. 4 Thorpe DM. Curr Pain Headache Rep. 2001 8 5 McMillan et al. Cancer Nurs. 2000 The Opioid Induced Constipation (OIC) opportunity Of the $14.8 billion global opioid market, five markets $14.8 account for ~80% of total unit volume: US (49%), UK (14%), Germany (5%), Canada (5), France (5%).1 PCPs and Billion Pain Managgpement Specialists comp rise the maj jyority of prescribers in these markets.2 In these five markets, there are 69 million patients taking 69 opioids for chronic pain (>30 days treatment) .3 For these chronic pain opioid users, opioid induced constipation Million (OIC) is the most common side effect. 4, 5 28-35 Approximately 40–50% (28-35 million) patients taking 1, 2, 3 Million* opioids for long-term pain develop constipation. 11-18 About 40–50% (11-18 million) of those OIC sufferers achieve th e d esi red t reat ment out comes with current Million* options that include OTC and Rx laxatives.6, 7 1 IMS Health MIDAS MAT-2Q12 2 IMS Health NPA MAT-2Q12, Cegedim MAT-2Q11) 3IMS patient level data MAT-2Q09IMS patient level data MAT-2Q09 4 Panchal, S et al. Opioid-Induced Bowel Dysfunction: Prevalence, Pathophysiology and Burden. Int J Clin Pract. 2007;61(7):1181-1187. 5 Reimer, K et al. Meeting the Challenges of Opioid-Induced Constipation in Chronic Pain Management – A Novel Approach. Pharmacology. 2009;83:10–17. 6 Pappagallo, M. (2001). Incidence, prevalence, and management of opioid bowel. 9 dysfunction. Am J Surg 182(5A Suppl), 11S−18S. 7 Holzer Regulatory Peptides 155 (2009) 11-17. *Number of patients in major opioid markets Competitive landscape for OIC Peripherally Acting mu-Opioid Receptor Antagonists: RELISTOR (methylnaltrexone bromide) SQ - Salix/Progenics • Indicated for OIC in patients with advanced medical illness who are receiving palliative care, when response to laxative therapy has not been sufficient • Introduced in 2008 RELISTOR (methlynaltrexone bromide) SQ - Salix/Progenics • ItitdfiInvestigated for use in non-chihronic non-cancer paititithOICin patients with OIC • CRL July 2012 RELISTOR (methlynaltrexone bromide) Oral - Salix/Progenics • Pre-registration Bevenopran (formerly CB-5945) – Cubist • Phase 2 complete, Phase 3 anticipated EOY 2012 TD-1211 – Theravance • Phase 2 recruitment compp;leted; seeking gp partner to commence Phase 3 Naldemedine (formerly S297995) – Shionogi • Phase 2b recruitment delays; Phase 3 start anticipated 2013 ______________________________________________ Amitiza (lubiprostone) Oral – Sucampo [chloride channel activator] • Approved for Chronic Constipation • sNDA for Opioid Bowel Disease (OBD) filed July 2012, granted fast track review for potential launch Q2 2013 OIC from a Customer Perspective: Patients, Physicians, Payers 11 Source: Patient quotes are from qualitative interviews with US OIC patients, August 2012. HCP quotes are from qualitative interviews with US HCPs, October 2009.; Payor quote from qualitative interviews with US payors, January 2012. Naloxegol An overview of the molecule and development Naloxegol MhiMechanism of fAti Action • Opioids bind to mu-opioid receptors located throughout the body (including bibrain an d gu t)1 • When opioids bind to mu-opioid receptors in the brain the outcome is pain relief1 • When opioids bind to mu-opioid receptors in the GI tract/gut the outcome is decreased GI motility which may lead to constipation1, 2, 3, 4 Naloxegol-chemical structure • Naloxegol is a PEGylated mu-opioid antitthtblkthiidtthtagonist that blocks the opioid at the receptor site in the gut.5 • Due to PEGyyplation, uptake of naloxeg ol across the Blood-Brain Barrier is limited6 1 Gutstein HB et al Goodman & Gilman’s; The Pharmacological Basis of Therapeutics, 10th ed. New York, McGraw-Hill 2001; 569-620 2Holzer P. Opioid receptors in the gastrointestinal tract. Regul Pept. 155(1-3); 2009; 11-17 3Kurz A and Sessler DI.
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